Subclinical Inflammation: Causes

Pathogenesis (disease development)

(Subclinical) inflammation (“silent inflammation”) is an expression of an innate (nonspecific) immune response of the organism. Endogenous and/or exogenous stimuli (see etiology/causes below) that compromise physiologic processes are the cause of inflammation. In the course of metabolization, e.g. conjugation of polar and hydrophilic substances (e.g. glucuronization, methylation, etc.), molecules are consumed for endogenous detoxification, which are no longer available in sufficient quantities for the “neutralization” of exogenous noxae. The inflammation (inflammation) triggered by metabolism is called metaflammation. Subclinical inflammation and its effects (proinflammatory cytokines (proinflammatory proteins that regulate cell growth and differentiation): IL-1ß, IL-6, IL-8, TNF-α, IFN-y) together with oxidative and nitrosative stress are part of a circulus vitiosus (“Vicious cycle” according to M. Pall, 2007). Furthermore, mitochondriopathy (diseases caused by mitochondrial dysfunction or damage) must be included in this event. LPS-induced (LPS = lipopolysaccharides; endotoxin) processes via intestine and the dental oral cavity system (LPS is released when gram-negative bacteria die, e.g., in periodontitis) activate a molecular complex that upregulates gene expression of the inflammatory cytokines TNF-alpha, IL1-beta, and IL-6 via the NFkB signaling chain. Furthermore, NFkB-mediated gene activation can trigger the expression of inducible nitric oxide synthase. This closes the circle: nitric oxide synthase catalyzes the formation of nitric oxide (NO) from the amino acid arginine and thereby induces the formation of reactive nitrogen radicals, the overproduction of which in turn triggers nitrosative stress and mitochondriopathies.LPS in serum is considered a marker of subclinical inflammation. LPS stimulates adipocytes, which in turn increase expression of the enzyme 11β-hydroxy-steroid dehydrogenase-1 (11β-HSD-1), which is considered a key enzyme in glucocorticoid metabolism. It plays a central role in regulating adipocyte cell differentiation and maturation. A marked increase in this enzyme is associated with increased abdominal/visceral truncal central body fat. Endotoxemia (“poisoning” caused by bacterial decay) may result from increased bacterial translocation of endotoxins:

Increased bacterial translocation of endotoxins from the gut may be due to:

  • High-fat diet (uptake of LPS with chylomicrons/lipoprotein particles secreted from the small intestine via the lymph into the bloodstream).
  • Leaky gut syndrome (increased intestinal permeability) [is controversial].
  • Disturbed balance of intestinal flora (dysbiosis) (here: overgrowth with gram-negative bacteria).

Bacterial or viral infections activate proinflammatory cytokines and NO (iNOS) activated by TH-1 cytokines. The aforementioned proinflammatory cytokines can trigger local or systemic inflammatory responses. Cytokines and their effects

Cytokine(s) Effect
IL-1ß, IL-6, TNF-α Proinflammatory
IL-8 Chemotactic recruitment of leukocytes.
IL-10 Antiinflammatory
IL-12 Differentiation of TH1 cells

Etiology (causes)

Biographical causes

  • Genetic burden from parents, grandparents (genetic conditions)?
  • Occupations – occupations associated with exogenous noxious agents (allergens, pollutants, etc.).

Behavioral causes

  • Nutrition
    • Increased intake of saturated fatty acis (SFA).
    • Increased intake of foods with high glycemic index → increase in NF-κB activation and NF-κB binding in mononuclear cells.
    • Consumption of contaminated foods (e.g., pesticides, heavy metals, etc.).
    • Consumption of processed food / processed food (eg, food additives).
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Consumption of stimulants
    • Tobacco (smoking)
  • Physical activity
    • Extreme physical work
  • Psycho-social situation
    • Stress
  • Overweight (BMI ≥ 25; obesity).
  • Android body fat distribution, i.e., abdominal/visceral, truncal, central body fat (apple type) – there is a high waist circumference or waist-to-hip ratio (THQ; waist-to-hip-ratio (WHR)); see “Adipose tissue as an endocrine organ” – esp. Fetuin A, tumor necrosis factor (TNF-alpha), IL-6, and other cytokines When measuring waist circumference according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
    • Men <94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

Disease-related causes

Laboratory diagnoses – laboratory parameters considered independent risk factors.

  • CRP (C-reactive protein) or hs-CRP (high-sensitivity (high-sensitivity) CRP).
  • LPS (lipopolysaccharides)
  • Fasting insulin > 17 mU/l
  • Triglycerides (hypertriglyceridemia)

Medication

  • Cytostatics (substances that inhibit cell growth or cell division).

X-rays

  • Radiation therapy (radiotherapy, radiatio)
  • Ionizing rays

Environmental pollution – intoxications (poisonings).

  • Air pollutants: particulate matter
  • Hazardous working materials
  • Plastics
  • Pesticides / insecticides
  • Heavy metals